Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P05231 (interleukin-6)
 23,907 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Effects of several cytokines on des-gamma-carboxy prothrombin (PIVKA II) synthesis in human hepatoma cells were investigated to know the process of PIVKA II production during a liver allograft rejection. Human recombinant interleukin-6 (IL-6) significantly stimulated the PIVKA II synthesis without any influence on the cell proliferation. The effect was almost completely neutralized by the specific anti-IL-6 antibody. Neither tumor necrosis factor (TNF), interleukin-1 (IL-1) nor interferon-gamma (IFN-gamma) had such a stimulative effect. IL-6 appears to stimulate PIVKA II production, and would be a candidate of factors that enhance the production of PIVKA II during a liver allograft rejection.
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PMID:The effect of IL-6 on the des-gamma-carboxy prothrombin synthesis in human hepatoma cells. 133 90

To study the mechanisms of hepatocyte injury, we examined serum interleukin-6 (IL-6) level in acute hepatitis patients. Based on their clinical features, these patients were divided into three groups, acute hepatitis (AH), severe acute hepatitis, and fulminant hepatic failure (FHF). The present study demonstrated that, in association with their clinical status, their serum IL-6 levels were gradually increased (16.5 +/- 14.5 pg/ml in AH, 26.3 +/- 19.0 pg/ml in severe AH, and 470.2 +/- 261.4 pg/ml in FHF; control level, 5.2 +/- 0.6 pg/ml). Furthermore, we found that a significant correlation between serum IL-6 level and prothrombin time existed in these patients and that the elevated serum IL-6 returned to a normal range after recovery from their hepatocyte injury. Thus, our study demonstrates that the serum IL-6 level is a possible marker for identifying the clinical status in acute hepatitis and that this cytokine may have some roles in hepatocyte injury.
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PMID:Elevated serum interleukin-6 levels in patients with acute hepatitis. 140 Sep

Recent studies in alcoholic hepatitis have proposed a role for the cytokine tumour necrosis factor-alpha (TNF-alpha) a mediator of endotoxic shock in sepsis. In this study plasma levels of the closely related cytokine interleukin-6 (IL-6) were assayed in 96 samples from 58 patients with severe alcoholic hepatitis, and 69 patients in control groups (21 normal, 10 alcoholic without liver disease, 10 inactive alcoholic cirrhosis, 18 chronic liver disease, 10 chronic renal failure). Plasma IL-6 levels were markedly elevated in patients with alcoholic hepatitis when compared with all control groups (P less than 0.001). IL-6 levels were higher in patients who died (P = 0.04) and correlated with the features of severe disease including: increased grade of encephalopathy, increased neutrophil count, increased prothrombin ratio, hypotension, increased serum creatinine and increased serum bilirubin. Surprisingly, no correlation was found between levels of plasma IL-6 and plasma TNF-alpha or endotoxin, or the presence of infection; an inverse correlation was found between plasma IL-6 and serum globulins. These findings provide further evidence that the IL-6/TNF cytokine system is activated in severe alcoholic hepatitis and may mediate hepatic or extra-hepatic tissue damage.
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PMID:Elevated plasma interleukin-6 and increased severity and mortality in alcoholic hepatitis. 204 24

Circulating levels of the proinflammatory cytokines interleukin-6 (IL-6), IL-8, and tumor necrosis factor-alpha (TNF-alpha) were measured in 13 children with autoimmune hepatitis (AIH) (seven with type 1 and six with type 2). In untreated children with type 1 AIH, TNF-alpha, IL-6, and IL-8 levels were elevated when compared to those of healthy controls (p < 0.005, p < 0.02, p = 0.06, respectively), whereas in children with type 2 AIH, cytokine levels were normal in all except one sample. A significant decrease in circulating IL-6, IL-8, and TNF-alpha was observed when patients were evaluated during a subsequent remission. We found no significant correlation of cytokine levels with alanine aminotransferase (ALT) activity, total serum gamma-globulins, or prothrombin activity. In patients with cirrhosis, serum IL-8 and IL-6 levels were higher (significantly in the case of IL-8) than those of patients without cirrhosis. In conclusion, activation of the in vivo production of the proinflammatory cytokines IL-6, IL-8, and TNF-alpha appears to be associated with type 1 but not with type 2 AIH.
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PMID:Circulating levels of interleukin-6, interleukin-8, and tumor necrosis factor-alpha in children with autoimmune hepatitis. 788 14

To assess the effect of interleukin-6 (IL-6) on the coagulation and the fibrinolytic systems, we administered a single subcutaneous injection of recombinant glycosylated human interleukin-6 (r-hIL-6) 100 micrograms per kg body weight) to four baboons (Papio ursinus). Four saline injected baboons served as controls. In serial plasma or serum samples collected over a period of seven days we measured several key parameters of the coagulation and the fibrinolytic systems, IL-6 and a set of acute phase proteins. Three hours after the injection, the serum IL-6 levels peaked at 50 ng/ml and then gradually declined with a terminal half-life of around 4 hours. The biological efficacy was demonstrated by the significant increases of several acute phase proteins, circulating platelets and the decrease of prealbumin and fibronectin. Between days 1 and 3, marked effects on the coagulation system were observed with a prolongation of the activated partial thromboplastin time, prothrombin time and thrombin time. Plasma concentrations of fibrinopeptide A and D-dimer increased. The antithrombin III antigen and activity levels decreased, but the thrombin-antithrombin III complex concentrations did not change. The fibrinolytic system rapidly showed striking modifications after 6-8 hours, the concentrations of tissue-type plasminogen activator and of plasminogen activator inhibitor type 1 peaked at respectively four and thirty times the basal concentrations. No changes were seen in the control group. We conclude that besides its well-known acute phase inducing and hematopoietic activities, subcutaneous rhIL-6 also modulates several parameters of the coagulation and the fibrinolytic systems.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:In vivo modulation of coagulation and fibrinolysis by recombinant glycosylated human interleukin-6 in baboons. 794 65

Tumor necrosis factor (TNF) is considered to be a pivotal mediator of endotoxin-induced lethality. To assess the intermediate role of TNF in specific systemic inflammatory responses known to contribute to tissue injury in endotoxemia, eight healthy adult chimpanzees were intravenously injected with Escherichia coli endotoxin (4 ng/kg). In four of these animals the administration of endotoxin was followed immediately by a bolus intravenous injection of an anti-TNF monoclonal antibody (15 mg/kg). Treatment with anti-TNF completely prevented the endotoxin-induced increase in serum TNF activity, and profoundly reduced the appearance of interleukin-6 and -8 (both P < .05). Neutrophilia and lymphopenia were not affected by anti-TNF, whereas neutrophil degranulation, as measured by the plasma concentrations of elastase-alpha 1-antitrypsin complexes, was only slightly reduced (peak levels after endotoxin alone 31.0 +/- 3.4 ng/mL, versus 25.5 +/- 3.4 ng/mL after endotoxin with anti-TNF; P < .05). Anti-TNF did not influence endotoxin-induced activation of the coagulation system, as reflected by unchanged increases in the plasma concentrations of the prothrombin fragment F1 + 2 and thrombin-antithrombin III complexes. In contrast, anti-TNF strongly attenuated the activation of the fibrinolytic system, ie, peak plasma levels of plasmin-alpha 2-antiplasmin were 33.8 +/- 11.1 nmol/L after endotoxin alone and 17.0 +/- 2.9 nmol/L after endotoxin with anti-TNF (P < .05). These results suggest that TNF is not the common mediator of systemic inflammatory changes in low-grade endotoxemia. Moreover, the finding that in this mild model anti-TNF specifically inhibited fibrinolysis suggests that treatment with anti-TNF potentially may enhance the tendency towards microvascular thrombosis in sepsis.
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PMID:Differential effects of anti-tumor necrosis factor monoclonal antibodies on systemic inflammatory responses in experimental endotoxemia in chimpanzees. 828 42

The formation of proplatelet-like processes on megakaryocytes cultured in vitro has been shown to be inhibited by prothrombin, found residually in human serum, which is converted in culture to thrombin. This study reports that another factor found in human serum will counter this inhibition and permit proplatelet-like process formation to occur in vitro even in the presence of inhibitory concentrations of thrombin. The factor was purified from human platelet lysates and identified by amino acid sequence analysis as the proteoglycan serglycin. A similar, if not identical, factor was found at elevated levels in the plasma of thrombocytopenic rabbits. Serglycin probably functions as a proplatelet potentiator by virtue of a tendency to complex with thrombin. Thrombin in complex with serglycin retains its enzymatic properties, but is apparently sterically hindered from interacting with the megakaryocyte cell surface. In preliminary studies, the in vivo administration of serglycin in mice resulted in an increased number of circulating platelets when given in combination with interleukin-6 (IL-6).
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PMID:The effect of the platelet-derived glycosaminoglycan serglycin on in vitro proplatelet-like process formation. 833 Jun 53

Thirteen coagulation tests evaluating hemostatic and fibrinolytic indices and serum cytokine and plasma endotoxin concentrations were obtained in 34 foals with a positive sepsis score (septic group) and 46 age-matched healthy foals. Compared to healthy foals, the prothrombin, activated partial thromboplastin, and whole blood recalcification times were significantly longer in septic foals. The fibrinogen and fibrin degradation products concentrations, percent plasminogen, alpha-2 antiplasmin, and plasminogen activator inhibitor activities, and tumor necrosis factor and interleukin-6 activities were greater in septic foals. Protein C antigen and antithrombin III activity were significantly lower in septic foals. Blood cultures were positive for growth and endotoxin was detected in 19 of 29 and 15 of 30 septic foals, respectively. In septicemic foals with detectable endotoxin in the plasma, the prothrombin and activated partial thromboplastin times were significantly longer and the plasminogen and antithrombin III activities were significantly less than in septic foals in which endotoxin was not detected. Twenty-three of the 34 septic foals did not survive. Septic foals that did not survive were most likely to have a positive blood culture in which a gram-negative organism was isolated. Histopathologic evidence of hemorrhage was evident in 11 foals at postmortem examination and thrombosis was identified in 2 foals. The prothrombin time was significantly longer in foals that had multisite hemorrhage at postmortem examination. The results of this study indicate that clinically relevant alternations in hemostatic and fibrinolytic indices occur in neonatal foals with septicemia and that derangements can be correlated with the presence of endotoxin in plasma. Derangements in hemostatic or fibrinolytic indices were helpful in identification of septic foals with increased risk of coagulopathy, but were not helpful in predicting hemorrhage as compared to thrombus formation. Survival of septicemic foals was correlated with gram-negative bacteremia, but not with the presence of endotoxin or coagulopathy.
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PMID:Hemostatic and fibrinolytic indices in neonatal foals with presumed septicemia. 950 57

Activation and inhibition of coagulation and fibrinolysis was analyzed in bronchoalveolar lavage (BAL) fluids obtained from endotoxin-challenged chimpanzees. The mediatory role of tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) on endotoxin-induced changes in bronchoalveolar coagulation and fibrinolysis was investigated in experiments in which the infusion of endotoxin was combined with the administration of monoclonal anti-TNF-alpha or anti-IL-6 antibodies. Endotoxin infusion elicited a marked increase in bronchoalveolar thrombin generation as measured by levels of prothrombin activation fragment F1+2 and thrombin-antithrombin complexes. Markers for intrinsic pathway activation were not detectable, suggesting that the thrombin generation was mediated by the tissue factor-dependent route. Levels of antithrombin were low before the injection of endotoxin and not detectable hereafter. The administration of anti-IL-6 antibody completely abolished the endotoxin-induced activation of bronchoalveolar coagulation, whereas treatment with anti-TNF-alpha antibody only partly inhibited this effect. Bronchoalveolar fibrinolytic activity, due to urokinase-type plasminogen activator (u-PA), was significantly depressed after endotoxin injection, mainly due to a striking increase in plasminogen activator inhibitor-2 levels in BAL fluid. The endotoxin-induced effects on bronchoalveolar fibrinolysis could be blocked by the simultaneous administration of anti- TNF-alpha antibodies. We conclude that endotoxemia results in the activation of bronchoalveolar coagulation, which is apparently mediated by the tissue factor route of coagulation activation and which may be amplified by consumption of antithrombin III. Bronchoalveolar fibrinolytic activity is significantly abolished by increased levels of mainly PAI-2 after the injection of endotoxin. The endotoxin-induced effects on bronchoalveolar coagulation appears to be mediated by IL-6, whereas TNF-alpha seems to be the pivotal mediator of the endotoxin-induced depression of bronchoalveolar fibrinolysis.
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PMID:Differential effects of anti-cytokine treatment on bronchoalveolar hemostasis in endotoxemic chimpanzees. 965 12

The purpose of this study was to evaluate the role of the sinusoidal endothelial cell (SEC) during the clinical course of alcoholic hepatitis. Twenty consenting patients (mean age: 49.4 +/- 11.0 years) with moderate or severe hepatitis were studied. The patients were selected and characterized according to their history of drinking and laboratory profile, including serum aminotransferases, bilirubin, total white blood cell and neutrophil count, and prothrombin times. C-reactive protein and interleukin-6 were also measured as markers of the hepatic acute phase response. A marker of the SEC functional state, the circulating level of hyaluronan, was measured in parallel with the circulating levels of soluble intercellular adhesion molecule (sICAM)-1 over a 6-month observation period. All patients were hospitalized for the first month and encouraged to abstain from drinking for the duration of the study. The initial increased levels of both hyaluronan (542 +/- 32 ng x ml(-1) serum) and sICAM-1 (488 +/- 70 ng x ml(-1) serum), gradually fell during the 6-month observation period, eventually reaching values close to those seen in healthy subjects. A positive correlation was obtained between changes in these two markers of SEC function/activation on the one hand, and between these two tests and bilirubin, on the other hand. These data indicate that abnormalities of SEC function/activation, as reflected by serum hyaluronan and siCAM-1, are prominent in alcoholic hepatitis, and these alterations improve within relatively short periods of time after cessation of alcohol consumption.
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PMID:Hyperhyaluronanemia in alcoholic hepatitis is associated with increased levels of circulating soluble intercellular adhesion molecule-1. 975 49


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